NDRG2 gene expression pattern in ovarian cancer and its specific roles in inhibiting cancer cell proliferation and suppressing cancer cell apoptosis.

BACKGROUND: The cancer cell metastasis and the acquisition of chemotherapy resistance remain huge challenge for ovarian cancer treatment. Previously, N-myc downstream-regulated gene 2 (NDRG2) serves as a tumor suppressor for many cancers. Here, we attempted to investigate the specific roles of NDRG2 in ovarian cancer. METHODS: The expression levels of NDRG2 were detected by qRT-PCR or Immunoblotting. CCK-8 assay was employed to examine the cell viability of ovarian cancer cells. The colony formation ability was determined by colony formation assay. Flow cytometry analyses were performed to detect the cell apoptosis and cell cycle. Xenograft tumor assay was performed to detect the in vivo function of NDRG2. RESULTS: We revealed that NDRG2 mRNA expression and protein levels were downregulated within both ovarian cancer tissues and cell lines. The overexpression of NDRG2 dramatically inhibited the cell viability and colony formation and tumor growth, whereas promoted the cell apoptosis, cell cycle arrest in G1 phase within ovarian cancer cells. More importantly, NDRG2 overexpression significantly enhanced the suppressive roles of cisplatin (DDP) in ovarian cancer cell viability. On the contrary, NDRG2 silence exerted opposing effects on ovarian cancer cells. CONCLUSIONS: In summary, we provide a solid experimental basis demonstrating the tumor-suppressive effects of NDRG2 in inhibiting the cell proliferation, enhancing the cell apoptosis, eliciting the cell cycle arrest in G1 phase, and promoting the suppressive effects of DDP on the viability of ovarian cancer cells. NDRG2 administration presents a potent adjuvant treatment for ovarian cancer therapy.

KCNQ1OT1 promotes ovarian cancer progression via modulating MIR-142-5p/CAPN10 axis.

BACKGROUND: Long non-coding RNA (lncRNA) has been regarded as crucial regulator for cancer progression. Roles of KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) in cancers including osteosarcoma and colon cancer have been previously reported. However, its role in ovarian cancer (OC) remains unclear. METHODS: Expression level of KCNQ1OT1 on OC cells and normal cell was analyzed with quantitative real-time PCR. Gain and loss-of-function experiments were performed to analyze the biological roles of KCNQ1OT1 in OC. Moreover, whether KCNQ1OT1 functions its role via mediating MICRORNA-142-5p (MIR-142-5p)/calpain 10 (CAPN10) axis was analyzed. In addition, effects of KCNQ1OT1, MIR-142-5p, and CAPN10 on overall survival of OC patients were analyzed at Kaplan-Meier plotter website. RESULTS: We showed KCNQ1OT1 was elevated expression in OC cells and indicated poorer overall survival of OC patients. Besides, we found KCNQ1OT1 could promote OC cell proliferation and migration in vitro. Moreover, MIR-142-5p was found reduced expression, while CAPN10 was found elevated expression in OC cells compared with normal cell. Kaplan-Meier curve analysis showed low MIR-142-5p or high CAPN10 expression were indicators for poorer overall survival of OC patients. At length, we showed KCNQ1OT1 could regulate OC development via MIR-142-5p/CAPN10 axis. CONCLUSIONS: Taken together, KCNQ1OT1 upregulates CAPN10 expression via sponging MIR-142-5p, thus promoting the proliferation and migration of OC.

Comparison between Serum HE4 and CA125 as Tumor Markers in Premenopausal Women with Benign Pelvic Mass.

BACKGROUND: The aim of the study was to evaluate the role of human epididymal secretory protein (HE4), cancer antigen 125 (CA125), and the Risk of Ovarian Malignancy Algorithm (ROMA) in diagnosing benign pelvic masses in premenopausal women. METHODS: Serum was collected from 391 premenopausal women with benign pelvic mass prior to surgery and from 45 healthy individuals. Serum HE4 and CA125 levels and ROMA scores were evaluated separately. RESULTS: Among the 391 women with benign pelvic mass, 2.3% (9/391) had elevated HE4 levels (> 70 pmol/L), while 37.1% (145/391) had elevated CA125 levels (> 35 U/mL) (p < 0001). Endometriosis provided false-positive results for CA125 levels in more than half of the cases but resulted in no significant change for HE4 level. In 13 gravid women with a mass, 30.8% (4/13) and 38.5% (5/13) had elevated HE4 and CA125 levels, respectively; however, the difference was not significant (p > 0.05). Moreover, serum levels and patient percentages for CA125 elevation significantly increased with increase in mass diameter, whereas those for HE4 did not. CONCLUSIONS: CA125 elevation showed random results for benign pelvic masses, while HE4 elevation showed a higher specificity. Thus, serum HE4 testing is a better approach than CA125 testing for diagnosing benign pelvic masses in premenopausal women.

Suppression of placental metallothionein 1 and zinc transporter 1 mRNA expressions contributes to fetal heart malformations caused by maternal zinc deficiency.

Zinc has been implicated to have a protective role against heart malformations during fetal development. Metallothionein 1 (MT-1) and zinc transporter 1 (ZnT-1) are two major metabolic factors that are associated with zinc metabolism. The present work aimed to investigate the association of placental MT-1 and ZnT-1 expressions with fetal heart malformations resulting from maternal zinc deficiency. Sprague-Dawley female rats were randomly divided into five groups of extremely low-zinc, low-zinc, moderately low-zinc, marginally low-zinc and normal zinc (n = 9-12), and were fed diets with controlled zinc content at 1.0 ± 0.3, 8.4 ± 1.8, 15.4 ± 2.8, 22.4 ± 4.1 and 29.4 ± 5.3 [mean ± standard deviation (SD)] mg of zinc/kg, respectively, from day 25 of preconception until day 19 of gestation. The female rats were bred, their fetuses were harvested at day 19 of gestation after killing the dams, and fetal hearts were morphologically examined. Zinc concentration and alkaline phosphatase (ALP) activity in maternal venous blood sera were tested, and MT-1 and ZnT-1 mRNA expressions in the placenta were assayed. Zinc concentrations and ALP activities in the blood were low in all zinc-deficient diet groups in a dose-dependent fashion. The incidences of heart malformations were increased, and the levels of placental MT-1 and ZnT-1 mRNA expressions were decreased in the extremely low-zinc, low-zinc and moderately low-zinc groups compared with the normal zinc group. Specifically, mRNA levels of placental MT-1 or ZnT-1 were significantly decreased and were lower than the specific threshold values in the fetuses with heart malformations but not in the fetuses without heart malformations in all the groups. These data indicate that maternal zinc deficiency resulted in an elevated incidence of fetal heart malformations, which was associated with significant decreases in placental MT-1 and ZnT-1 mRNA expressions to the levels below the threshold values that may be a crucial factor to determine the presence of fetal heart malformations.

Zinc antagonizes homocysteine-induced fetal heart defects in rats.

It has been suggested that zinc may have a protective role against heart defects during fetal development. We investigated the effects of zinc on the development of fetal cardiac malformations induced by homocysteine. Pregnant Sprague-Dawley rats were randomized into one of five groups: control (C), homocysteine (H), homocysteine + zinc (Z), homocysteine + folic acid (F), or homocysteine + zinc + folic acid (ZF) (each n = 8). Homocysteine (8 nmol/day) was administered intraperitoneally in the H, Z, F, and ZF groups on gestation days (GD) 8, 9, and 10. Zinc (30 mg/kg day), folic acid (30 mg/kg day), or both (30 mg/kg day each) were administered intragastrically daily in the Z, F, and ZF groups, respectively, throughout the pregnancy. In each group, two fetuses were removed on GD 13, 15, 17, and 19 and examined for cardiac malformations; maternal copper/zinc-containing-superoxide dismutase (Cu/Zn-SOD) activity and metallothionein type I (MT-1) mRNA expression were measured simultaneously. The prevalence of cardiac malformations was significantly higher in group H than in group C, and significantly lower in group Z than in group H at the studied time points. Cu/Zn-SOD activity and MT-1 mRNA levels were significantly lower in group H than in group C, and significantly higher in group Z than in group H. Our data suggest that zinc antagonizes homocysteine-induced teratogenic effects on the fetal heart, possibly via the inhibition of excessive peroxidation.